Determinants of Exercise Intolerance in Postural Orthostatic Tachycardia Syndrome: a Systematic Review, 2024, Gerardina Abbate et al

Abstract
Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a syndrome of an exaggerated heart rate (HR) response with standing, disproportionately affecting young women associated with exercise intolerance due to dizziness, palpitations, and/or chest pain.
Research question: How does the exaggerated increase in HR with standing translate into impaired exercise tolerance in subjects with POTS?

Aims: To systematically analyze determinants of exercise intolerance in subjects with POTS.

Methods: We searched the National Library of Science and identified 11 cohorts with a diagnosis of POTS and an assessment of exercise capacity. We abstracted the information including type of exercise testing, hemodynamics and gas exchange parameters (peak oxygen consumption [VO2]) with exercise, and effect of interventions (if present).

Results: We identified 849 subjects with POTS, female:male ratio of 8.5:1, 25±8 years, and 365 age-and sex-matched controls. A cycle ergometer was used in 8 studies (574 subjects, 68%) and a treadmill in 3 (275 subjects, 32%). Peak VO2 was measured in 10 studies (836 subjects, 98%), and exercise hemodynamics in 9 (593 subjects, 70%). All 11 (100%) studies described a higher HR at rest and during submaximal exercise in subjects with POTS, with a similar slope of HR/load, and shorter time to peak HR. Of the 9 studies with hemodynamics, 6 (67%) reported a reduction in stroke volume (SV) with standing and with exercise, but only 1 (11%) documented a reduction in cardiac output (CO). Two studies (22%) enrolling teenagers showed a variable increase in SV and CO in POTS. Peak VO2 was reduced in 8 (80%) studies when compared with predicted values, but only in 4
(40%) when compared with controls matched for deconditioning. Intravenous fluid administration in two studies did not affect HR, SV, CO or peak VO2. Exercise training in one study (19 subjects) and propranolol 20 mg in another study (11 subjects) led to improving peak VO2.

Conclusions: An exaggerated HR response with standing and with exercise is a hallmark of POTS, a mechanism by which subjects reach a higher HR at lower workloads. While the increase in HR is associated with a reduction in SV, CO is typically maintained and occasionally increased, therefore making it an unlikely mechanism responsible for the peculiar exertional symptoms of POTS. Strategies that result in a reduction in HR may, on the other hand, translate in improved exercise capacity in subjects with POTS.
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